Our studies show that expression of the neural cell adhesion molecule L1 can be regulated by action potential stimulation, by controlling levels of L1 mRNA. Regulation is selective for specific frequencies of stimulation, and for specific types of neural cell adhesion molecules (NCAM is not affected). Adhesion of neuroblastoma cells to DRG axons is reduced after 5 days electrical stimulation at the frequency that is effective in lowering L1 expression, but no changes in cell-cell adhesion are produced by stimulus patterns that do not alter L1 levels. Association of Schwann cells with axons is reduced for up to 4 days after stimulation at 0.1 Hz, but not after 1 Hz stimulation. Fasciculation of neurites can be regulated by impulse activity at an appropriate frequency. Intracellular signaling from neural impulses can be sensitive to temporal features of action potential stimulation, rather than to the concentration of second messengers or products in signaling reactions activated by the stimulus. Transcription of the c-fos gene can be more strongly activated by action potential stimuli producing low amplitude intracellular calcium transients repeated at short intervals, compared to action potential bursts that produce much larger intracellular calcium transients, repeated at less frequent intervals. Phosphorylation of the transcription factor CREB at Ser 133, does not correlate with c-fos transcription for some patterns of stimulation, particularly those consisting of intense bursts repeated at longer intervals. Accommodation of growth cones to electrically-induced collapse is associated with a decrease in trans-membrane calcium currents, which results from removal of calcium channels from the cell membrane after 24 hours of action potential stimulation at appropriate frequencies. Growth cone responses to action potentials involve different intracellular calcium signaling pathways than those activated by the receptor-mediated growth cone collapsing factor NI-35.